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Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Toxicological and metabolic considerations for histone deacetylase inhibitors

Joanna Fraczek1, Tamara Vanhaecke, Vera Rogiers

  • 1VUB, Toxicology, Laarbeeklaan 103, Brussels 1090, Belgium. jfraczek@vub.ac.be

Expert Opinion on Drug Metabolism & Toxicology
|January 5, 2013
PubMed
Abstract

Insights

Histone deacetylase inhibitors (HDIs) show anticancer promise, but their in vivo efficacy depends on absorption, distribution, metabolism, and excretion. Further research into formulations, preclinical characterization, isoform targeting, and patient selection can improve HDI therapy.

Area of Science:

  • Pharmacology
  • Oncology
  • Drug Development

Background:

  • Vorinostat and romidepsin are the first histone deacetylase inhibitors (HDACi or HDIs) to show anticancer potential in clinical trials.
  • Demonstrating in vitro antitumor activity of HDIs is straightforward, but in vivo efficacy is challenging due to complex pharmacokinetic factors.

Purpose of the Study:

  • To summarize clinical data on the pharmacokinetic properties of HDIs in advanced clinical development.
  • To provide an overview of HDI metabolic pathways and related adverse effects.

Main Methods:

  • Review of clinical data on HDIs.
  • Analysis of pharmacokinetic properties, including metabolism.
  • Compilation of adverse effect profiles.

Main Results:

  • Clinical data on pharmacokinetics of advanced-stage HDIs are summarized.
  • Metabolic pathways and adverse effects of HDIs are detailed.

Conclusions:

  • HDIs represent a promising therapeutic class, but efficacy and safety can be enhanced.
  • Improvements include better formulations, extensive preclinical disposition characterization, targeting specific deacetylase isoforms, and molecular signature-based patient selection.

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